Action Points

Recent use of some oral contraceptives is associated with an increased risk of breast cancer.

Point out that the risk of breast cancer varied with formulation of the contraceptives, and those with low-dose estrogen were not associated with cancer.

Recent use of some oral contraceptives is associated with an increased risk of breast cancer, researchers reported.

In a nested case-control study, women who had used birth control pills within the previous year had a 50% increase in the risk of disease, compared with those who had never or formerly used the drugs, according to Elisabeth Beaber, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

But the risk varied with formulation of the contraceptives; some types -- notably those with low-dose estrogen -- were not associated with cancer, Beaber and colleagues reported in the Aug. 1 issue of Cancer Research.

In women under 50, she told MedPage Today, "their absolute risk of breast cancer is less than 2%."

But while that risk "raises red flags," the main concern is not oral contraceptives, she said, but familial and genetic predispositions, such as mutations in the BRCA genes. Those factors, she noted, were not analyzed in the study.

Pederson added that it's "important to reinforce to our patients that the most commonly used birth control pill -- low-dose [estrogen] monophasic -- was even in this study not associated with an increased risk."

The issue is not a new one, Beaber and colleagues noted: a 1996 pooled analysis of more than 150,000 women, a third of them with breast cancer, showed a slight increase in risk associated with oral contraceptives.

But most such studies have relied on participant recall, lacked data on current contraceptive formulations, and didn't stratify breast cancer risk by estrogen receptor status, they noted.

To help fill the gap, Beaber and colleagues turned to the records of the Group Health Cooperative, an integrated health care delivery system in the Seattle-Puget Sound area.

They conducted a nested case-control study among women 20 to 49 who had been enrolled in the system for at least a year before a breast cancer diagnosis or (for controls) a similar date between January 1990 and October 2009.

For the study, "recent use" of oral contraceptives was defined as within the previous 12 months.

All told, the study included 1,102 women with cancer and 21,952 controls matched to the cases on age, year, enrollment length, and medical chart availability.

The researchers used the system's electronic health records to abstract data on contraceptive use and classified the drugs according to combinations of estrogen and progestin components, doses, and monophasic or triphasic dosing schedule.

The bottom line, they reported, was that oral contraceptive use in the previous year was associated with a odds ratio for breast cancer of 1.5, with a 95% confidence interval from 1.3 to 1.9, compared with women who had formerly or never used the medications.

Other findings related to recent use of oral contraceptives included:

High-dose estrogen was associated with an odds ratio for cancer of 2.7

Ethynodiol diacetate was associated with an odds ratio of 2.6

Triphasic dosing with an average of 0.75 milligrams of norethindrone was associated with an odds ratio of 3.1

Other types, including low-dose estrogen oral contraceptives, were not linked to an increased risk, they reported.

The odds ratio for estrogen receptor–positive disease was 1.7 (with a 95% confidence interval from 1.3 to 2.1), while for estrogen receptor-negative disease it was 1.2, with a 95% confidence interval from 0.8 to 1.8. The difference between the two was not significantly different, Beaber and colleagues reported.

"Our results suggest that use of contemporary oral contraceptives in the past year is associated with an increased breast cancer risk relative to never or former oral contraceptive use," Beaber said in a statement, adding the risk "may vary by oral contraceptive formulation."

Beaber cautioned that the results need confirmation and "should be interpreted cautiously."

She noted that breast cancer remains rare in young women and that oral contraceptives have "numerous established health benefits" that need to be considered as well by doctors and patients.

Those benefits include reproductive planning, menses regulation, decreased dysmenorrhea, and decreased risk of benign breast conditions, she and colleagues concluded.

She and colleagues cautioned that the study is limited by the restricted exposure length that could be evaluated, owing to relatively short durations of continuous enrollment in the Group Health Cooperative system.

As well, data on some potentially relevant confounding factors weren't available for all women, and some statistically significant associations might still be the result of chance, since many analyses were conducted.

The study was supported by the National Cancer Institute. Beaber disclosed no relevant relationships.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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